In joint sites such as knees, cartilage tissues present in a joint with mobility on an inner side of synovial membrane is made up of type II collagen, proteoglycan, water, etc. Such cartilage tissues are defined as articular cartilages (hyaline cartilages). On the other hand, cartilage tissues present outside joint sites contain, as constituents, more type I collagen than type II collagen.
The articular cartilage has a poor ability for repair. Accordingly, once the articular cartilage is damaged, it is almost impossible to naturally regenerate the articular cartilage. In cases where a patient has a traumatic damage of articular cartilage and repeatedly suffers a severe pain and/or hydrarthrosis, the patient is treated with an analgesic medication for oral administration and/or intra-articular injection of hyaluronic acid. However, these treatments are symptomatic treatments and not a curative treatment. Accordingly, a current general treatment method for the articular cartilage is a method in which the articular cartilage is surgically regenerated. Non-Patent Literature 1 discloses bone trepanation and osteochondral autograft transplantation. These are well-known as main surgical treatment methods.
The bone trepanation disclosed in Non-Patent Literature 1 is a method including the steps of (i) drilling a bone in a damaged cartilage region so as to cause bleeding from bone marrow and (ii) leading mesenchymal stem cells (MSCs) contained in the bone marrow to the damaged cartilage region, in expectation of regeneration of a cartilage and a tissue which is similar to the cartilage. This method can be easily implemented under arthroscopy, without sacrifice of tissues of a patient himself/herself. Therefore, this method is widely employed as a primary treatment method for cartilage damage in the world.
Herein, stem cells are cells having a self-replication ability and a differentiation ability. Well-known examples of such stem cells encompass embryonic stem cells (ES cells), induced pluripotent stem cells (iPS cells), and somatic stem cells. Examples of the somatic stem cells encompass hematopoietic stem cells, neural stem cells, and mesenchymal stem cells. The ES cells and the iPS cells have multipotency which allows the ES cells and the iPS cells to differentiate into any tissues. The hematopoietic stem cells have an ability to differentiate into blood cells, and the neural stem cells have an ability to differentiate into nerve cells. Further, the mesenchymal stem cells are present in tissues of bone marrow etc., and are known as stem cells which have multipotency to differentiate into adipose cells, bone cells, chondrocytes, and the like cells.
The osteochondral autograft transplantation disclosed in Non-Patent Literature 1 is a method in which a cylindrical mass including a bone and a cartilage is taken from a healthy region of autologous joint cartilage, and then autografted into a site of damage. This method allows repair at the site of damage with a transplanted hyaline cartilage and a fibro cartilage which is in a gap of the transplanted hyaline cartilage. However, it is a drawback of the method that tissues in the healthy region are damaged and an area for transplantation is limited.
Further, as another surgical treatment method for articular cartilage damage, autologous chondrocyte transplantation is known. This autologous chondrocyte transplantation is a method reported by Brittberg et al. in 1994. According to the method, a small amount of a cartilage tissue is obtained from an unloaded site of knee articular cartilage of a patient himself/herself and chondrocytes are isolated and monolayer-cultured. Then, thus cultured chondrocytes are transplanted to a site of cartilage damage.
As still another surgical treatment method for articular cartilage damage, a treatment method utilizing tissue engineering as disclosed in Patent Literature 1. In this treatment method, a cell source such as chondrocytes, stem cell, or like cells and a scaffold material are transplanted together with each other to a site of articular cartilage damage, and thereby regeneration of an articular cartilage is promoted.
Further, human stem cell clinical research of a “treatment method using a three-dimensional tissue-engineered construct derived from autologous synovial mesenchymal stem cells, for articular chondral lesions” (research plan approved on Jan. 25, 2012) is being implemented at Osaka University Hospital. The subject of this clinical research is patients with traumatic knee cartilage damage. In this clinical research, first, synovial membrane stem cells isolated from an intra-articular tissue are cultured. Then, a biological stimulus is given to thus cultured cells, so that a three-dimensional tissue fragment is obtained. Thereafter, the tissue fragment is transplanted to a site of cartilage damage.